The focus of the proposed research is continued genotype and phenotype studies of families who demonstrate autosomal dominant transmission of dyslexia. Dyslexia is linked to chromosome 15 markers in some of these families, but not in others, indicating genetic heterogeneity. The specific long-term objectives of this project are (1) to more precisely map the dyslexia locus on chromosome 15 and to evaluate whether there is a second major dyslexia locus on another chromosome in families not linked to chromosome 15; (2) to clarify the development of both the underlying linguistic phenotype and components of the reading process in dyslexics from these families; (3) to test for any phenotypic differences between genotypically different dyslexics; and (4) to determine whether there is continuity in the underlying linguistic phenotype from preschool to adulthood, and, if so, to determine how this underlying deficit affects reading processes at different ages. Because of the unique advantages of developmental studies within dyslexic families with a common etiology, the proposed research will yield a much clearer picture of dyslexic development across the life-span than has previously been possible. Achieving these objectives will lead to a clearer, scientific understanding of the effects of one (or more) major genes on a specific and culturally significant aspect of human cognition. Clinically, such an understanding will form the basis of a well- grounded approach to early identification and treatment of this common developmental disorder. The methodology that is proposed to meet these objectives consists of (1) continued linkage studies of both old and new families in collaboration with Shelley Smith and Bill Kimberling in Omaha; (2) a cross-sectional study of both the underlying linguistic phenotype and the components of the reading process in adolescent and child dyslexics from these families; and (3) a longitudinal study of the underlying linguistic phenotype in preschool children to determine which aspect of this phenotype is most predictive of later dyslexia in these high-risk families.